Drug overdose is now the leading cause of injury death among adults in the U.S. This dramatic shift has been attributed to opioid analgesic overdose; deaths from opioid analgesics have exceeded the combined overdose deaths from heroin and cocaine since 2003. Addressing opioid overdose is consistent with the White House goal of reducing drug-induced morbidity and mortality by 15%. San Francisco, a city with historically high rates of opioid use and related morbidity and mortality, implemented city-wide distribution of naloxone (the short- acting opioid antagonist) in 2004, which has been associated with a substantial decline in heroin-related death. However, during this period opioid analgesic overdose deaths have increased in San Francisco. From 2010 to early 2012, 253 out of 261 opioid overdose deaths were due to opioid analgesics and 47% of these decedents were primary care patients of the San Francisco Department of Public Health (DPH). Three-quarters of those decedents were being prescribed chronic opioids and thus were eligible for a Pain Management Registry (PMR) of all patients receiving chronic opioids now maintained in selected clinics. DPH is initiating a program for prescription of take-home naloxone from primary care clinics, providing a unique opportunity to assess the implementation of a naloxone program targeting opioid analgesic users. While ecologic and epidemiologic studies have demonstrated the apparent effectiveness of naloxone distribution in reducing illicit opioid overdose, no studies have evaluated the capacity to implement and evaluate clinic-based naloxone prescription targeting opioid analgesic users. We propose an exploratory study to measure the feasibility of naloxone prescription from multi-provider primary care clinics in a safety net health care system, the acceptability to patients and providers of naloxone prescription, and the validity of electroni medical records (EMR) as a means to evaluate such programs. To maximize naloxone uptake and standardize quality of naloxone delivery during roll-out, trained research staff will provide technical assistance and capacity building to staff in clinics and associated pharmacies leading up to, and during, the execution of the clinic-based naloxone program. These trainings will educate key stakeholders about the program, provide support and problem-solve issues with the rollout (i.e., availability at the pharmacy, knowledge of indications, etc.), and optimize implementation of clinic-based naloxone prescription. The program will be implemented in a staggered fashion across six DPH clinics and data will be analyzed in steps-time periods corresponding with dates of pre- and post-rollout periods of naloxone at each clinic. The primary outcomes will be the proportion of PMR patients prescribed naloxone within 3 visits of the start date in each clinic. Results will also include a detailed survey of patients and brief surveys of prescribers and pharmacists regarding acceptability of naloxone prescription. Finally, an assessment of the validity of EMR data for evaluating this program will be conducted, comparing results by ICD-9 coding to direct chart review of patient emergency department visits.